Barley beta-glucan promotes MnSOD expression and enhances angiogenesis under oxidative microenvironment.
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ABSTRACT: Manganese superoxide dismutase (MnSOD), a foremost antioxidant enzyme, plays a key role in angiogenesis. Barley-derived (1.3) ?-d-glucan (?-d-glucan) is a natural water-soluble polysaccharide with antioxidant properties. To explore the effects of ?-d-glucan on MnSOD-related angiogenesis under oxidative stress, we tested epigenetic mechanisms underlying modulation of MnSOD level in human umbilical vein endothelial cells (HUVECs) and angiogenesis in vitro and in vivo. Long-term treatment of HUVECs with 3% w/v ?-d-glucan significantly increased the level of MnSOD by 200% ± 2% compared to control and by 50% ± 4% compared to untreated H2 O2 -stressed cells. ?-d-glucan-treated HUVECs displayed greater angiogenic ability. In vivo, 24 hrs-treatment with 3% w/v ?-d-glucan rescued vasculogenesis in Tg (kdrl: EGFP) s843Tg zebrafish embryos exposed to oxidative microenvironment. HUVECs overexpressing MnSOD demonstrated an increased activity of endothelial nitric oxide synthase (eNOS), reduced load of superoxide anion (O2 (-) ) and an increased survival under oxidative stress. In addition, ?-d-glucan prevented the rise of hypoxia inducible factor (HIF)1-? under oxidative stress. The level of histone H4 acetylation was significantly increased by ?-d-glucan. Increasing histone acetylation by sodium butyrate, an inhibitor of class I histone deacetylases (HDACs I), did not activate MnSOD-related angiogenesis and did not impair ?-d-glucan effects. In conclusion, 3% w/v ?-d-glucan activates endothelial expression of MnSOD independent of histone acetylation level, thereby leading to adequate removal of O2 (-) , cell survival and angiogenic response to oxidative stress. The identification of dietary ?-d-glucan as activator of MnSOD-related angiogenesis might lead to the development of nutritional approaches for the prevention of ischemic remodelling and heart failure.
SUBMITTER: Agostini S
PROVIDER: S-EPMC4288365 | biostudies-literature | 2015 Jan
REPOSITORIES: biostudies-literature
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